It is proposed to use an animal model to learn about the relationship of situs inversus viscerum to congenital heart malformations. Preliminary work in this laboratory has shown that mouse embryos homozygous for an autosomal recessive gene causing situs inversus have a relatively high incidence of congenital heart malformations which show a striking resemblance to those in human patients with asplenia syndrome. Mice with this mutation will be used in the following studies: 1. A systematic, detailed investigation of cardiac and non-cardiac malformations in order to define the similarity of the animal model to the human disease. 2. Examination of embryos and fetuses in various stages of development to learn about the morphogenetic steps giving rise to these malformations. 3. Investigation of the effects of changes in genetic background on the expressivity of the situs inversus gene in causing cardiac malformations, since there is some evidence that genetic background may affect the incidence and possibly pattern of these cardiovascular malformations. These studies are relevant to human disease since individuals with situs inversus have a much higher incidence of cardiac malformations than do those with normal situs. In addition, it can be hypothesized that the asplenia syndrome and its variants are expressions of homozygosity for situs inversus in human patients.